Development of a Biodegradable, Water-Resistant Tissue Adhesive based on Mussel Adhesive Proteins Wound closure continues to be one of the most important parts of all surgical procedures. Every operation requires proper wound closure to ensure timely wound healing and protection from complications such as infection, wound dehiscence, and sinus formation in the wound closure line. Although traditional suturing and stapling are the most commonly used methods, in certain cases these wound closure devices may not be ideal and the use of a tissue adhesive is desired. Because tissue adhesives are required to be biocompatible, adhere in an aqueous/physiological environment, and biodegradable into nontoxic byproducts, they have proved difficult to engineer. Although the FDA has recently approved two tissue adhesives for certain applications in the U.S. and scientists continue to develop new adhesives and sealants, none of them have yet been proven ideal. Thus, there remains a great need for improved surgical glues. Nature often provides inspiration for the development of new technologies, and adhesive proteins secreted by marine mussels provide ample inspiration for the development of new medical adhesives. Marine mussels can anchor themselves to various surfaces in a turbulent, saline environment through the release of adhesive proteins that harden rapidly. One of the most intriguing components found in these adhesives is the relatively unusual amino acid, 3,4-dihidroxyphenylalanine (DOPA), which is believed to be responsible for both moisture-resistant adhesion and cohesive hardening of these adhesive proteins. DOPA-containing adhesives, both natural and synthetic, have been shown to bind strongly to surfaces ranging from biological tissues to various metals. In developing a new tissue adhesive, we are combining the unique adhesive and cohesive properties of DOPA with a biocompatible and biodegradable polymeric backbone to create a novel degradable and water-resistant tissue adhesive. This proposal outlines the synthesis and characterization of a hydrolysable polyethylene glycol (PEG)-based polymer modified with DOPA. By changing the molecular weights of the starting material PEG, we hope to enhance the cohesive properties and overall adhesive strength over adhesives we have developed in the past. Experiments will be performed to determine the feasibility of manufacturing this adhesive polymer and of its function as a medical glue. Development ofa Biodegradable, Water-Resistant Tissue Adhesive based on Mussel Adhesive Proteins Effective surgical glues have advantages over traditional wound closure devices in simplifying complex surgical procedures and in reducing surgical time, which can expediteproper wound healing. However, due to stringent design requirements such as water-resistant adhesion, biocompatibility, and degradability, successful tissue adhesives have been difficult to engineer. The development and evaluation of a new biodegradable tissue adhesive that combines a marine adhesive moiety and a biocompatible synthetic polymer is described here. [unreadable] [unreadable] [unreadable]